title: Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer.
abstract: Colorectal cancer (CRC) is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. MicroRNAs (miRNAs) are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p) revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC.
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Clinic for Cancer, Surgery and Transplantation, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Kristina
authors.initials: K
authors.lastname: Schee
authors.forename: Susanne
authors.initials: S
authors.lastname: Lorenz
authors.forename: Merete Molton
authors.initials: MM
authors.lastname: Worren
authors.forename: Clara-Cecilie
authors.initials: CC
authors.lastname: Günther
authors.forename: Marit
authors.initials: M
authors.lastname: Holden
authors.forename: Eivind
authors.initials: E
authors.lastname: Hovig
authors.forename: Oystein
authors.initials: O
authors.lastname: Fodstad
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Meza-Zepeda
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs